Research into the effects of cannabinoid on brain function has become of increased relevance with respect to potential clinical uses of marijuana, for example: appetite enhancement in AIDS patients, and relief of nausea associated with chemotherapy. In addition, widespread """"""""recreational"""""""" use/abuse of marijuana also necessitates better understanding of cannabinoid's effects, especially those on cognitive function. The overarching tenet of this proposal pertains to the comparison of systemic with local cannabinoid administration to reveal global, as opposed to regional, mechanisms of cannabinoid, and cannabinoid receptor involvement in memory formation. This will be achieved by combining hippocampal ensemble recordings with pharmacological manipulation in two distinct behavioral paradigms:(DNMS) and open-field water maze. Both tasks require on-line processing of multimodal information during working to short-term memory processing (DNMS task) and short-term to long-term memory processing (water maze). To this end, electrode-recording arrays implanted into the dentate gyrus/CA3 should reveal differentiation of functions in processes of encoding, consolidation, and memory recall. ? ? The initiation of a collaborative effort between Wake Forest University Health Sciences and the University of Aberdeen, has aided the technical refinement of site-directed infusion targeting the same brain region that is under electrophysiological investigation. Results from agonist infusions will confirm and extend previous systemic studies, such that learning-related alterations can be pinpointed to the hippocampal cannabinoid system. While initial work using acute administration of cannabinoid receptor agonists and antagonists will establish the principal involvement of the cannabinoid system in memory formation, a more meaningful elucidation of consequences of frequent medicinal or recreational use will be provided by studies of chronic (28 day) cannabinoid exposure. This will permit a better physiological, pharmacological, and psychological understanding of mechanisms of tolerance. The strength of this approach is consistency between dose, vehicle and route of administration for the acute and chronic, systemic and local infusion studies, paired with established behavioral paradigms that are well suited to dissecting various stages of memory processing. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA008549-09
Application #
6727952
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (06))
Program Officer
Volman, Susan
Project Start
1995-03-15
Project End
2009-02-28
Budget Start
2004-06-10
Budget End
2005-02-28
Support Year
9
Fiscal Year
2004
Total Cost
$254,223
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Physiology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Goonawardena, Anushka V; Plano, Andrea; Robinson, Lianne et al. (2015) Modulation of food consumption and sleep-wake cycle in mice by the neutral CB1 antagonist ABD459. Behav Pharmacol 26:289-303
Hampson, Robert E; Fuqua, Joshua L; Huettl, Peter F et al. (2013) Conformal ceramic electrodes that record glutamate release and corresponding neural activity in primate prefrontal cortex. Conf Proc IEEE Eng Med Biol Soc 2013:5954-7
Taghva, Alexander; Song, Dong; Hampson, Robert E et al. (2012) Determination of relevant neuron-neuron connections for neural prosthetics using time-delayed mutual information: tutorial and preliminary results. World Neurosurg 78:618-30
Robinson, Lianne; Platt, Bettina; Riedel, Gernot (2011) Involvement of the cholinergic system in conditioning and perceptual memory. Behav Brain Res 221:443-65
Opris, Ioan; Hampson, Robert E; Stanford, Terrence R et al. (2011) Neural activity in frontal cortical cell layers: evidence for columnar sensorimotor processing. J Cogn Neurosci 23:1507-21
Goonawardena, Anushka V; Sesay, John; Sexton, Cheryl Ann et al. (2011) Pharmacological elevation of anandamide impairs short-term memory by altering the neurophysiology in the hippocampus. Neuropharmacology 61:1016-25
Goonawardena, Anushka V; Riedel, Gernot; Hampson, Robert E (2011) Cannabinoids alter spontaneous firing, bursting, and cell synchrony of hippocampal principal cells. Hippocampus 21:520-31
Howlett, Allyn C; Reggio, Patricia H; Childers, Steven R et al. (2011) Endocannabinoid tone versus constitutive activity of cannabinoid receptors. Br J Pharmacol 163:1329-43
Marmarelis, V Z; Shin, D C; Song, D et al. (2011) Dynamic nonlinear modeling of interactions between neuronal ensembles using principal dynamic modes. Conf Proc IEEE Eng Med Biol Soc 2011:3334-7
Hampson, Robert E; Miller, Frances; Palchik, Guillermo et al. (2011) Cannabinoid receptor activation modifies NMDA receptor mediated release of intracellular calcium: implications for endocannabinoid control of hippocampal neural plasticity. Neuropharmacology 60:944-52

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